Hemorrhoids are one of man's main afflictions. Homo sapiens pays this price, hemorrhoids, for its primate ancestor, Pithecanthropus erectus, stood up in contrast to his other non-human primates and other mammalian species wherein hemorrhoids do not occur. Hemorrhoidal syndromes are a condition with great morbidity but fortunately minimal mortality, albeit frequent bothersome symptoms and complications.
"Hemorrhoids", often referred to as "piles" or "almorranas" by Hispanics, are truly enlarged veins in the area around the anus, anatomically known as the hemorrhoidal plexi. These veins constitute the external and the internal hemorrhoids. The hemorrhoidal plexus is formed by the anastomosis of two distinct venous systems; the systemic via the inferior vena cava and the hepatic via the portal vein. Whichever venous system has an increase in its pressure, permanent or intermittent, will cause varicose dilation of the hemorrhoidal veins. The most common etiology for the former venous system is right sided congestive heart failure while for the latter, is caused by cirrhosis of the liver with portal hypertension. Unfortunately, both types of clinical syndromes are commonly associated with hemorrhoidal complications often affecting these chronically, very ill patients. However, hemorrhoidal syndromes are very common even in the absence of the aforementioned venous hypertension entities.
Signs and symptoms of the hemorrhoidal syndrome are variable and result from the "swollen" (enlarged) hemorrhoidal veins in and around the anus and rectum, respectively labeled external and internal hemorrhoidal syndromes. Although the presence of these dilated veins may be asymptomatic, many patients complain of passing bright red blood covering the stool, or noticing blood on the toilet paper or toilet bowl. Internal hemorrhoids may protrude through the anus becoming irritated and painful and pathologically having a severe cellular inflammatory response in the contiguous tissues. External hemorrhoids may likewise include an inflammatory response in the anal mucosa and may include a painful selling or hard lump, particularly with a thrombus (clot), around the anus. Excessive straining, rubbing or cleaning around the anus may cause further irritation and inflammation with generation of free radical species to further the painful symptoms, with consequent bleeding, itching, and draining mucus, a true curse of the inflammation and distention of these veins.
Although hemorrhoidal symptoms may subside within a few days, many cases are associated with local and rectal complications, including fissures, fistulae, abscesses or irritation and itching (so called pruritus ani). The inflammatory reactions are chronic, indolent and infected. Not infrequently these patients succumb to one or another of the available surgical treatments. Surgical therapies include electrical or coagulation laser or infrared photocoagulation to "burn" the hemorrhoids; rubber band ligation to cut off circulation; sclerotherapy to shrink these veins by injecting agents that "scar" these veins or by surgical removal, hemorrhoidectomy. All these primitive and advanced methods may be averted by proper preventive measures and therapeutic applications such as reparative sitz baths and the use of local ointments, creams, lotions, patches and suppositories with both therapeutic anti-inflammatory agents, vaso-constrictors, and synergistic anti-oxidants as in this patent application to reduce inflammation, swelling and free radical species damage to the putative ano-rectal tissues and hemorrhoidal veins.
In addition to the hemorrhoidal syndromes, there are other important anal inflammatory conditions. Inflammations of the anal conduit (canal) are variously called anusitis, cryptitis and papillitis, usually caused by alterations in the rhythm of defecation, that is, alternating periods of constipation and diarrhea, the latter with its variations in stool pH and fecal chemical constituents, such as the presence of active digestive enzymes. Alterations in fecal micro-flora, gastrointestinal infections and parasitic infestations, particularly pinworm, are responsible for anal inflammation, whereby the antioxidant complex of the present invention in appropriate delivery vehicles may be an adjunct to therapy of ano-rectal diseases.
Another common and very painful condition is anal fissure, which is a linear ulcerating lesion in the anal canal. This is purportedly tabulated as the most painful anal inflammatory condition. Pruritus ani is another common syndrome accompanied by intractable itching and local inflammation resulting from hemorrhoids, local infections, dermatologic diseases and pinworm disease among the most common. The intense itching leads to excoriations, ulcerations and complicating inflammation with secondary infections.
Other causes of ano-rectal inflammation are sexually transmitted diseases and perianal infections and abscesses. The later often originate from a suppurative cryptitis, or from a fissure. Fistula-in-ano may result from a perianal abscess and is a chronic, indolent and painful condition. Inflammation is most prominent and requires antibiotics and drainage with local care including topical analgesics. The present antioxidant preparations would be an important adjunct in the symptomatic and reparative management of these ano-rectal inflammations.
There are a number of patents which have been issued for compositions and methods of treating hemorrhoids and related ano-rectal wounds. Topical formulations not only treat hemorrhoidal pain but also sphincter spasm and related symptoms. Gallina in U.S. Pat. No. 5,234,914 dated Aug. 10, 1993, taught a method of applying to ano-rectal tissues and to hemorrhoids a composition which included hyaluronic acid or its salts in amounts ranging from 0.1 to 10% by weight, in acceptable carriers. The uses of hyaluronic acid included its anti-inflammatory and wound healing properties for ano-rectal conditions and diseases,
Packman and Oskman described the use of hemorrhoidal compositions containing disaccharide polysulfate-aluminum compounds, like sucralfate in U.S. Pat. No. 5,196,405, Mar. 23, 1993. This method of alleviating hemorrhoidal symptoms included sucralfate alone or in combination with antibiotics, anti-fungal agents or local anesthetics in an attempt to ameliorate ano-rectal symptoms and heal the putative wounds. Compositions could also include anti-inflammatory agents, steroids, and/or vaso-constrictors, causing a complex matrix to be formed between the wound and the sucralfate in order to promote a prolonged adhesion of the preparation to the affected tissue.
U.S. Pat. No. 4,761,285, dated Aug. 2, 1988, taught various compositions for the relief of hemorrhoidal symptoms and the treatment of hemorrhoids. It taught a preparation comprising leptandra's culver root, chick peas, and grape seeds. The latter are now known to contain proanthocynidins, antioxidants which are also present in pine bark extracts. These investigators enhanced their topical preparation with honey, cinnamon and oils. Okumura and associates more recently disclosed the use of prostaglandins in the therapy of hemorrhoids and wounds in U.S. Pat. No. 5,852,050 dated Dec. 22, 1998, which is herein incorporated by reference. Stable prostaglandins, as Geraprost, are used as oral or topical preparations because these prostaglandins improve peripheral blood circulation while inhibiting thrombus formation through a decrease in platelet aggregation.
U.S. Pat. No. 4,784,842 dated Nov. 15, 1988, disclosed a composition for treatment of abrasions and cuts comprising a terpene and a vitamin E compound. The preparation purportedly facilitated healing and reduced swelling, bleeding and pain by applying the mixture to the affected external area. Also taught are that the treatment mixture could be administered by aerosols for spraying. Similarly, as in the present invention, a suitable complex of antioxidants and minerals for adjuvant management of ano-rectal diseases may be administered by pump or mist spray packaging or by pressurized aerosols, according to the guidelines for propellants issued by the FDA.
In U.S. Pat. No. 4,613,498 dated Sep. 23, 1986, Crosby disclosed an external hemorrhoid medication as a petroleum jelly ointment. The reference taught a powdered mixture of alum, quinine sulfate and aspirin be applied topically to the affected area. Anderson, in U.S. Pat. No. 4,162,866 dated Mar. 11, 1980, taught an anorectal medication comprising glycerides and fragments of the ripe berry of the plant solanum carolinense (horse nettle). The reference also included sulfur, ammonium alum and turpentine. Earlier, Urbin, in U.S. Pat. No. RE28,O dated May 14, 1974 disclosed the use of oxidase enzymes to treat hemorrhoids, by destroying the amines formed by the fecal microflora in the colon.
U.S. Pat. No. 5,595,753, dated Jan. 21, 1997, taught the use of L-arginine for topical formulations for treating hemorrhoidal pain and sphincteric muscle spasm in gastrointestinal tract. Inflammation of the anal mucosa and hemorrhoids cause spasms of the internal anal sphincter with consequent ano-rectal pain. The pain associated with hemorrhoids is due primarily to the adjacent inflammatory reaction. Nitric oxide (NO) is a known modulator of sphincter tone, to which the amino acid L-arginine acts as a competitive inhibitor of compounds that block the action of NO production. Thus, L-arginine's use as taught in the '753 patent in topical preparations, alleviates anal pain by decreasing internal sphincter tone and thereby abolishing sphincter spasm. This amino acid does not participate as an antioxidant in the amelioration of the local inflammatory response, as proposed by the compositions of the present patent application.
Suppositories consisting of tissue respiratory factor as the active ingredient are known. Analgesic and anti-inflammatory compositions for topical applications were also disclosed by Reller and Kretschmar in U.S. Pat. No. 4,199,576, Apr. 22, 1980. The reference taught a number of salicylic acid derivatives as useful non-irritating topical anti-inflammatory agents which, like aspirin, are inhibitors of prostaglandin synthesis. Like the latter, histamine, serotonin, and the kinins are mediators of inflammation but with these the prostaglandins are continuously biosynthesized and released from the cells at the site of inflammation. Since prostaglandins have a longer effect in situ, it is suggested by the present invention that it is vital to decrease inflammation's free radical tissue damage with topical antioxidants plus the known anti-inflammatory agents like the salicylates, steroids and other derivatives so well known in the art of this industry.
Another common brand of hemorrhoidal suppositories and ointment is marketed under the trade name of Anusol. The composition includes pramoxine hydrochloride and zinc oxide, with the former containing bismuth subgallate and bismuth resorcin. Some preparations of Anusol also include hydrocortisone 1%. Their stated indications are for itching, burning and soreness of hemorrhoids and other minor ano-rectal discomfort and irritation.
There are many other over the counter ano-rectal products, but none contain the antioxidant complex of the present invention. They contain other topically beneficial ingredients for ano-rectal conditions, each with designated therapeutic goals, for example, vaso-constrictors and analgesics to decrease pain, itching, swelling, soreness or to diminish the size of the hemorrhoids or its bleeding complications. Some examples of these OTC products include americaine, balneol, calmol-y, cortex rectal itch ointment, diothane, epinephricaine, gentzy and tucks wipes, proctofoam, nupercainal, Vaseline, wyanoids, and many others. These all conform to Code of Federal Regulations 45-33576, dated May 22, 1980.
Local anesthetics such as benzocaine and related caines may be added to ameliorate discomfort and pain, and tissue respiratory factor, which also diminishes discomfort and stimulates fibroblast's metabolic functions to deposit collagen. As noted below, to enhance the healing of muco-cutaneous lesions, the present invention may also optionally add epidermal growth factor and/or other cellular growth factors and hormones, which stimulate epithelial cell growth, vital in the repair process to accelerate wound healing.
Various patents have been issued for both tissue protection and for repair of wounds. These compositions may also be used, but are not limited, to ano-rectal inflammatory wounds, surgeries and burns. Pickart in U.S. Pat. No. 5,554,375, dated Sep. 10, 1996, which is herein incorporated by reference, disclosed compositions for protecting irritated or damaged skin from further oxidative and biochemical damage, thereby allowing the repair process to progress. Many of these compositions accelerate the rate of healing of wounds and burns. Pickart taught for these uses complexes of peptone digests of various proteins, like soybean protein, with salts of copper, tin, and indium while the '090 patent of Okumura et al. disclosed the benefits of vasoconstrictors and inhibitors of clot formation with stable prostaglandins.
In summary, the main pharmacologic ingredients in these ano-rectal compositions include moisturizers, local anesthetics, such as benzocaine, dibucaine, pramoxine, lidocaine, tetracaine and others; vaso-constrictors such as ephedrine and epinephrine; nitrates to reduce anal sphincter spasm; protectants, such as aluminum hydroxide gel, calamine, cocoa butter, cod liver oil, glycerin, lanolin, mineral oil and others; and wound healing agents, as vitamins A and D, and zinc compounds, as noted. Astringents, antiseptics, keratolytic agents and anti-cholinergics may also be part of these therapeutic compositions.
Despite the impressive pharmacologic activity directed to reducing pain and promoting healing of ano-rectal conditions, no one has recognized the benefits that antioxidants can play and particularly, the benefits that can be derived from using the synergistic antioxidant complex of the present invention.
It is thus an object of the present invention to provide various compositions and methods of employing the present compositions for ameliorating and treating inflammatory ano-rectal conditions and hemorrhoidal syndromes. The preparations are designed to improve both signs and symptoms of ano-rectal diseases and aid in the repair processes of the aforementioned to avoid development of the distressing and debilitating complications of ano-rectal diseases and hemorrhoids.
These and further objects will be more readily appreciated when considering the following disclosure and appended claims.